FWF supports an international research project led by FH Upper Austria

The increasing resistance to antibiotics highlights the urgent need for alternative treatment methods for bacterial infections. Antibody‑based therapies are already successfully used in treating cancer and autoimmune diseases. The next step is to determine how these therapeutic approaches can also be applied to combat bacteria. FH‑Prof. PD Dr. Johannes Preiner from the Department of Medical Engineering at FH Upper Austria in Linz has now launched a new basic‑research project on this topic, funded by the FWF, in collaboration with partners in the Netherlands.

Significant progress in this field is currently limited by gaps in our understanding of the underlying molecular mechanisms. It is well established that IgM antibodies represent a class of antibodies that play a major role in defending against bacteria by activating the complement system. The complement system is an essential part of the human immune system and consists of more than two dozen proteins.

IgM antibodies are star‑shaped structures that undergo a change in their conformation when they bind to bacteria that need to be eliminated. However, the exact way in which this structural change occurs is still unknown to science, yet understanding this mechanism is essential for developing targeted therapies based on it.

High‑resolution microscopy as the foundation for experimental research
This is precisely where Johannes Preiner and his research team in Linz, together with a research group led by Suzan Rooijakkers at the University Medical Center in Utrecht, the Netherlands, are focusing their efforts. Their work involves a combination of several state‑of‑the‑art biophysical methods, including high‑speed atomic force microscopy, 3D single‑molecule fluorescence microscopy, and quartz crystal microbalance technology.

The researchers are optimistic due to recent studies highlighting the importance of IgM for human immunity against various pathogens, including the largely antibiotic‑resistant bacterium S. aureus as well as several SARS‑CoV‑2 variants. One key mechanism through which antibodies combat bacterial infections is the activation of the human complement system mentioned earlier, which possesses powerful tools to eliminate bacteria. When antibodies bind to the bacterial surface, this leads to the direct killing of bacteria by disrupting their membrane, as well as increased destruction of bacteria by the body’s own phagocytic cells.

Laying the groundwork for innovative therapies
“Based on the experimental results, we will also develop a mechanistic model of the underlying molecular interactions, thereby creating the foundation for optimizing IgM antibody development as well as pharmacokinetic and pharmacodynamic modeling,” explains project lead Johannes Preiner. This is directly connected to future immunotherapies.
“The prospect of helping to shape the foundations of a therapy that offers an alternative to antibiotic treatment is a strong motivation for everyone involved. After all, the extent of antibiotic resistance in many common bacterial strains has reached a truly alarming level,” Preiner says, describing his drive to generate scientific value with practical impact by the end of the project in 2028.

The research project “Determinants of IgM‑Mediated Complement Activation” is co‑funded by the Austrian Science Fund (FWF) and the State of Upper Austria through the Matching Funds Initiative. 

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